Gangliosides and/or related glycosphingolipids are implicated in numerous important biological functions and medical problems, including neural synaptic transmission, cell growth and differentiation, cancer, Tay-Sachs disease, and other lipid storage diseases. With the exception of the lipid storage diseases, little is known about the actual biochemical effects or the structural and mechanistic chemistry of these substances. Therefore, we are studying the chemistry of glycosphingolipids and their properties when bound in biomembranes and membrane-like preparations, for the purpose of providing basic knowledge which can contribute to the understandig and solution of medical problems. Our approaches are to study the nuclear magnetic resonance, particularly the carbon NMR, of these substances and their component sugars, using splitting, relaxation time, and other measurements to elucidate and compare their conformations, and how they change upon binding into membrane vesicles. The sugar groups distinguish this class of molecules from most other lipids, and so we are synthesizing molecules of varying lipid chain lengths and sugar groupings, in order to compare these with the naturally occurring substances. We are also synthesizing lipid molecules with photolabile groups incorporated in their structures for use as membrane photolabeling reagents. We are studying the hydrophobic binding properties of these substances by a novel technique using high-pressure liquid chromatography. We propose to study the effects of gangliosides and other glycosphingolipids on membrane fusion and ion permeation mechanisms.